POLR1D promotes colorectal cancer progression and predicts poor prognosis of patients. Issue 5 (20th January 2019)

• Record Type: Journal Article
• Authors: Wang, Mingqing; Niu, Wenbo; Hu, Rong; Wang, Yanjing; Liu, Yangyang; Liu, Lingyu; Zhong, Juan; Zhang, Cha; You, Haiyan; Zhang, Jiaxing; Lu, Lu; Wei, Lianbo; Xiao, Wei
• Is Part Of: Molecular carcinogenesis. Volume 58:Issue 5(2019)
• Page Start: 735
• Page End: 748
• Publication Date: 2019-01-20
• Subjects: β‐catenin -- cell cycle -- colorectal cancer -- p53 -- POLR1D; Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.22966
• Languages: English
• ISSNs: 0899-1987

Abstract

Abstract : RNA polymerase I subunit D (POLR1D), which is involved in synthesis of ribosomal RNA precursors and small RNAs, has been shown to be overexpressed in several human cancer types. Nevertheless, the role of POLR1D in the progression of colorectal cancer (CRC) remains unknown. The following study aimed to investigate the role and underlying mechanism of POLR1D in CRC progression. In this report, we found that POLR1D was significantly up‐regulated in CRC through data mining of oncomine database. Furthermore, the immunohistochemistry (IHC) staining of a tissue microarray (TMA) of 75 human CRC patients showed that the expression level of POLR1D was positively correlated to tumor size and poor survival of CRC patients. Aberrant expression of POLR1D significantly promoted cell proliferation and migration in vitro, as well as tumor growth in vivo. Conversely, POLR1D knockdown displayed the opposite effects. The flow Cytometry assays showed that POLR1D fostered cell cycle progression at G1‐S transition and inhibited cell apoptosis. Finally, at the molecular level, we demonstrated that POLR1D‐induced the promotion of G1‐S cell cycle transition was mediated by activation of wnt‐β‐catenin signaling and inactivation of p53 signaling. Our results suggested that POLR1D may function as a risk factor for predicting the outcome of CRC patients, as well as a potential therapeutic target for CRC.